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Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans

Stepien, Magdalena; Hughes, David J; Hybsier, Sandra; Bamia, Christina; Tjønneland, Anne; Overvad, Kim; Affret, Aurélie; His, Mathilde; Boutron-Ruault, Marie-Christine and Katzke, Verena, et al. (2017) In British Journal of Cancer 116(5). p.688-696
Abstract

BACKGROUND: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers.

METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance... (More)

BACKGROUND: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers.

METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk.

RESULTS: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13-0.98, Ptrend=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, Ptrend=0.8878) in multivariable models. The calculated Cu/Zn ratio showed a positive association for HCC (OR=4.63; 95% CI: 1.41-15.27, Ptrend=0.0135). For IHBC and GBTC, no significant associations were observed.

CONCLUSIONS: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.

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Aged, Biliary Tract Neoplasms/epidemiology, Carcinoma, Hepatocellular/epidemiology, Case-Control Studies, Copper/blood, Europe/epidemiology, Female, Humans, Liver Neoplasms/epidemiology, Male, Middle Aged, Prospective Studies, Zinc/blood
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British Journal of Cancer
volume
116
issue
5
pages
9 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:85011617240
ISSN
1532-1827
DOI
10.1038/bjc.2017.1
language
English
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yes
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2a6cada5-4721-413b-a436-b6e078744128
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2018-10-02 09:17:11
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2018-10-07 05:09:00
@article{2a6cada5-4721-413b-a436-b6e078744128,
  abstract     = {<p>BACKGROUND: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers.</p><p>METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk.</p><p>RESULTS: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13-0.98, Ptrend=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, Ptrend=0.8878) in multivariable models. The calculated Cu/Zn ratio showed a positive association for HCC (OR=4.63; 95% CI: 1.41-15.27, Ptrend=0.0135). For IHBC and GBTC, no significant associations were observed.</p><p>CONCLUSIONS: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.</p>},
  author       = {Stepien, Magdalena and Hughes, David J and Hybsier, Sandra and Bamia, Christina and Tjønneland, Anne and Overvad, Kim and Affret, Aurélie and His, Mathilde and Boutron-Ruault, Marie-Christine and Katzke, Verena and Kühn, Tilman and Aleksandrova, Krasimira and Trichopoulou, Antonia and Lagiou, Pagona and Orfanos, Phlippos and Palli, Domenico and Sieri, Sabina and Tumino, Rosario and Ricceri, Fulvio and Panico, Salvatore and Bueno-de-Mesquita, H B As and Peeters, Petra H and Weiderpass, Elisabete and Lasheras, Cristina and Bonet Bonet, Catalina and Molina-Portillo, Elena and Dorronsoro, Miren and Huerta, José María and Barricarte, Aurelio and Ohlsson, Bodil and Sjöberg, Klas and Werner, Mårten and Shungin, Dmitry and Wareham, Nick and Khaw, Kay-Tee and Travis, Ruth C and Freisling, Heinz and Cross, Amanda J and Schomburg, Lutz and Jenab, Mazda},
  issn         = {1532-1827},
  keyword      = {Aged,Biliary Tract Neoplasms/epidemiology,Carcinoma, Hepatocellular/epidemiology,Case-Control Studies,Copper/blood,Europe/epidemiology,Female,Humans,Liver Neoplasms/epidemiology,Male,Middle Aged,Prospective Studies,Zinc/blood},
  language     = {eng},
  number       = {5},
  pages        = {688--696},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans},
  url          = {http://dx.doi.org/10.1038/bjc.2017.1},
  volume       = {116},
  year         = {2017},
}